Molecular mimicry between neurons and an intracerebral pathogen induces a CD8 T cell-mediated autoimmune disease

Monica Sanchez-Ruiz, Laura Wilden, Werner Müller, Werner Stenzel, Anna Brunn, Hrvoje Miletic, Dirk Schlüter, Martina Deckert

    Research output: Contribution to journalArticlepeer-review


    To identify basic mechanisms of how infections may induce a neuron-specific autoimmune response, we generated mice expressing OVA as neuronal autoantigen under control of the neuron-specific enolase promoter (NSE-OVA mice). Intracerebral, but not systemic, infection with attenuated Listeria monocytogenes-secrcting OVA induced an atactic-paretic neurological syndrome in NSE-OVA mice after bacterial clearance from the brain, whereas wild-type mice remained healthy. Immunization with attenuated Listeria monocytogenes-secreting OVA before intracerebral infection strongly increased the number of intracerebral OVA-specific CD8 T cells aggravating neurological disease. T cell depletion and adoptive transfer experiments identified CD8 T cells as decisive mediators of the autoimmune disease. Importantly, NSE-OVA mice having received OVA-specific TCR transgenic CD8 T cells developed an accelerated, more severe, and extended neurological disease. Adoptively transferred pathogenic CD8 T cells specifically honied to OVA-expressing MHC class I + neurons and, corresponding to the clinical symptoms, ∼30% of neurons in the anterior horn of the spinal cord became apoptotic. Thus, molecular mimicry between a pathogen and neurons can induce a CD8 T cell-mediated neurological disease, with its severity being influenced by the frequency of specific CD8 T cells, and its induction, but not its symptomatic phase, requiring the intracerebral presence of the pathogen. Copyright © 2008 by The American Association of Immunologists, Inc.
    Original languageEnglish
    Pages (from-to)8421-8433
    Number of pages12
    JournalJournal of Immunology
    Issue number12
    Publication statusPublished - 2008


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